Format

Send to

Choose Destination
J Gen Virol. 2018 Jan 22. doi: 10.1099/jgv.0.001007. [Epub ahead of print]

Specific transcriptional and post-transcriptional regulation of the major immediate early ICP4 gene of GaHV-2 during the lytic, latent and reactivation phases.

Author information

1
1​Equipe Transcription et Lymphome Viro-Induit (TLVI), UMR 7261 CNRS, Université François Rabelais de Tours, UFR Sciences et Techniques, Parc de Grandmont, 37200 Tours, France.
2
2​Veterinary Integrated Research Unit, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), 5000 Namur, Belgium.
3
3​INRA, Département de Santé Animale, Centre de Recherches de Tours, 37380 Nouzilly, France.

Abstract

Transcriptional and post-transcriptional mechanisms are involved in the switch between the lytic, latent and reactivation phases of the viral cycle in herpesviruses. During the productive phases, herpesvirus gene expression is characterized by a temporally regulated cascade of immediate early (IE), early (E) and late (L) genes. In alphaherpesviruses, the major product of the IE ICP4 gene is a transcriptional regulator that initiates the cascade of gene expression that is essential for viral replication. In this study, we redefine the infected cell protein 4 (ICP4) gene of the oncogenic Marek's disease virus (MDV or gallid herpesvirus 2) as a 9438 nt gene ended with four alternative poly(A) signals and controlled by two alternative promoters containing essentially ubiquitous functional response elements (GC, TATA and CCAAT boxes). The distal promoter is associated with ICP4 gene expression during the lytic and the latent phases, whereas the proximal promoter is associated with the expression of this gene during the reactivation phase. Both promoters are regulated by DNA methylation during the viral cycle and are hypermethylated during latency. Transcript analyses showed ICP4 to consist of three exons and two introns, the alternative splicing of which is associated with five predicted nested ICP4ORFs. We show that the ICP4 gene is highly and specifically regulated by transcriptional and post-transcriptional mechanisms during the three phases of the GaHV-2 viral cycle, with a clear difference in expression between the lytic phase and reactivation from latency in our model.

PMID:
29458534
DOI:
10.1099/jgv.0.001007

Supplemental Content

Full text links

Icon for Ingenta plc
Loading ...
Support Center